Generalized Encapsulations of ZIF-Based Fe-N-C Catalysts with Controllable Nitrogen-Doped Carbon for Significantly-Improved Stability Toward Oxygen Reduction Reaction.

The vigorous development of efficient platinum group metal-free catalysts is considerably important to facilitate the universal application of proton exchange membrane fuel cells. Although nitrogen-coordinated atomic iron intercalated in carbon matrix (Fe-N-C) catalysts exhibit promising catalytic activity, the performance in fuel cells, especially the short lifetime, remains an obstacle. Herein, a highly-active Fe-N-C catalyst with a power density of >1 w cm-2 and prolonged discharge stability with a current density of 357 mA cm-2 after 40 h of constant voltage discharge at 0.7 V in H2 -O2 fuel cells using a controllable and efficient N-C coating strategy is developed. It is clarified that a thicker N-C coating may be more favorable to enhance the stability of Fe-N-C catalysts at the expense of their catalytic activity. The stability enhancement mechanism of the N-C coating strategy is proven to be the synergistic effect of reduced carbon corrosion and iron loss. It is believed that these findings can contribute to the development of Fe-N-C catalysts with high activity and long lifetimes.

Does heart failure increase the risk of incident cancer? A meta-analysis and systematic review.

Recently, several studies have demonstrated that heart failure (HF) may increase the risk of incident cancer. However, this association has not been statistically and systematically verified by any comprehensive pooled analyses. We performed a meta-analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer. From inception to April 2019, we searched PubMed and EMBASE for published relevant articles on patients with HF diagnosed with cancer afterwards, with reported outcomes of morbidity and mortality. Two investigators independently reviewed these included studies. Study data were independently extracted using predefined data extraction forms. Random and fixed-effects models were fit for the study duration. This analysis consisted of 4 cohort studies comprising 5,004,251 participants. The relative risk (RR) for incident cancer was 1.22 (95% confidence interval (CI), 1.13-1.33) indicating that patients with HF may have a higher risk of developing cancer. The pooled RR of co-mortality was 2.03 (95% CI, 1.13-3.65), indicating that HF associated with cancer increases the risk of mortality. In this meta-analysis and systematic review, our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality.

Case report: Retroperitoneal solid pseudopapillary neoplasm associated with multiple hepatic metastases.

Solid pseudopapillary neoplasm (SPN) is a rare tumor mostly occurring in the pancreas. They are low-grade malignant tumors of the exocrine pancreas that occasionally metastasize, usually to the liver or peritoneum. Additionally, multiple metastases of extrapancreatic SPN to the liver are extremely rare and have been reported before. This study presents a case of a 13-year-old male patient with retroperitoneal SPN and multiple hepatic metastases. The patient presented with abdominal trauma and underwent enhanced CT, which revealed upper pancreatic occupancy and three hypodense foci in the right lobe of the liver. Moreover, increased spleen size was noted. The patient's serum tumor marker CA125 was increased to 39.00 U/mL (N < 35.0 U/mL), and circulating tumor cells were elevated to 10.2 FU/3 mL (N < 8.7 FU/3 mL). The patient underwent retroperitoneal occupancy resection and splenectomy, followed by resection of liver metastases 7 months after the surgery. Furthermore, multiple liver metastases from retroperitoneal SPN were confirmed postoperatively. The patient recovered for 1 year without tumor recurrence. This case emphasizes the importance of evaluating serum tumor markers and medical imaging in young patients as well as the fact that surgery appears to be the preferred treatment option for multiple metastases in SPN.

Cryo-Shocked Platelet Coupled with ROS-Responsive Nanomedicine for Targeted Treatment of Thromboembolic Disease.

Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host-guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.

Virtual biopsy using CT radiomics for evaluation of disagreement in pathology between endoscopic biopsy and postoperative specimens in patients with gastric cancer: a dual-energy CT generalizability study.

PURPOSE: To develop a noninvasive radiomics-based nomogram for identification of disagreement in pathology between endoscopic biopsy and postoperative specimens in gastric cancer (GC). MATERIALS AND METHODS: This observational study recruited 181 GC patients who underwent pre-treatment computed tomography (CT) and divided them into a training set (n = 112, single-energy CT, SECT), a test set (n = 29, single-energy CT, SECT) and a validation cohort (n = 40, dual-energy CT, DECT). Radiomics signatures (RS) based on five machine learning algorithms were constructed from the venous-phase CT images. AUC and DeLong test were used to evaluate and compare the performance of the RS. We assessed the dual-energy generalization ability of the best RS. An individualized nomogram combined the best RS and clinical variables was developed, and its discrimination, calibration, and clinical usefulness were determined. RESULTS: RS obtained with support vector machine (SVM) showed promising predictive capability with AUC of 0.91 and 0.83 in the training and test sets, respectively. The AUC of the best RS in the DECT validation cohort (AUC, 0.71) was significantly lower than that of the training set (Delong test, p = 0.035). The clinical-radiomic nomogram accurately predicted pathologic disagreement in the training and test sets, fitting well in the calibration curves. Decision curve analysis confirmed the clinical usefulness of the nomogram. CONCLUSION: CT-based radiomics nomogram showed potential as a clinical aid for predicting pathologic disagreement status between biopsy samples and resected specimens in GC. When practicability and stability are considered, the SECT-based radiomics model is not recommended for DECT generalization. CRITICAL RELEVANCE STATEMENT: Radiomics can identify disagreement in pathology between endoscopic biopsy and postoperative specimen.

Preclinical studies of licorice in ulcerative colitis: A systematic review with meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice, as a traditional Chinese herbal medicine, possessing the efficacies of invigorating spleen and replenishing qi, heat-clearing and detoxicating, phlegm-resolving and cough suppressant, relieving spasm and pain, and hamonizing actions of various medicines. AIM OF THE STUDY: The goal of this systematic review, which includes meta-analysis and network pharmacology in preclinical studies, is to investigate the multiple efficacies of licorice on ulcerative colitis (UC). MATERIALS AND METHODS: We searched several databases, e.g., Web of Science, Elsevier ScienceDirect and PubMed until Januanry 2022 for literature collection, and the Review Manager 5.3 was used to analyze the data. To synthesize the retrieved data, the fixed and random-effects models were utilized, respectively, and network pharmacology was applied to confirm the mechanisms. RESULTS: Based on the result of meta-analysis, it suggested that the treatments of licorice extract and its active compounds showed strong therpeutic effects, which not only reflected the declining histological score, a index of the colitis severity [SMD = -2.86, 95% CI (-3.65, -2.08); P < 0.00001], but also reversed colonic shortness [WMD = 1.67, 95% CI (1.16, 2.19); P < 0.00001] between experimental UC model and licorice-treatment groups. In addition, it suggested the significant reduction of TNF-α level [SMD = -2.70, 95% CI (-3.23, -2.16); P < 0.00001], which acted as a crucial role in inflammatory response. Furthermore, from the results of network pharmacology, it indicated that anti-inflammation, anti-oxidative stress, immunomodulatory effect and microbiota homeostasis were the predominant therapeutic mechanisms of licorice extract and its active compounds treating UC. CONCLUSION: This systematic review with meta-analysis and network pharmacology demonstrates an efficient role of licorice extract and its active compounds in preclinical studies of UC, which provides supporting evidence for clinical trial implementation. However, there exist some limitations, such as technique quality decificency, missed reports due to negative outcome, failure to calculate sample size, and the risk of bias.

Coating Porous TiO2 Films on Carbon Nanotubes to Enhance the Durability of Ultrafine PtCo/CNT Nanocatalysts for the Oxygen Reduction Reaction.

The development of excellent activity and durability catalysts for the oxygen reduction reaction (ORR) is essential for the commercialization of proton exchange membrane fuel cells (PEMFCs). Reducing the size of catalyst particles can provide more reaction sites to mitigate the performance degradation caused by reduced platinum loading. However, at the same time, it makes the particles more prone to agglomeration and exfoliation, leading to a rapid reduction in catalyst activity. Here, we present the design of a composite support (TiO2/CNT) with a porous TiO2 film that immobilizes PtCo nanoparticles (NPs) loaded on the support while protecting the carbon nanotubes inside. The particle size of PtCo NPs was only 1.99 nm (determined by transmission electron microscopy), but the nanocatalyst (PtCo/TiO2/CNT) maintained high catalytic performance and stability on account of the strong metal support interaction (SMSI). PtCo/TiO2/CNT exhibited a high mass activity (MA, 0.476 A mgPt-1) and was found to have MA retention rates of 91.7 and 88.8% in durability tests performed at 0.6-1.0 V and 1.0-1.5 V, respectively.

A TiN@C core-shell support for improving Pt catalyst corrosion resistance.

The corrosion of the support in proton-exchange membrane fuel cells (PEMFCs) is a major obstacle to their development. In this study, we combined the excellent corrosion resistance and strong metal-support interaction (SMSI) provided by titanium nitride (TiN) with the excellent conductivity of carbon to construct a TiN@C composite support composed of a TiN core and a porous carbon nanolayer shell. The composite TiN@C support exhibited a higher corrosion resistance than the carbon support during testing at 1.2 V (vs. RHE) for 400 h. Based on X-ray photoelectron spectroscopy and density functional theory calculations, the improved corrosion resistance originated from the excellent corrosion resistance of titanium nitride itself and SMSI between Pt and N in TiN. Overall, the high corrosion resistance of the TiN@C support can significantly improve PEMFC durability.

Anti-inflammatory and immunomodulatory effects of baicalin in cerebrovascular and neurological disorders.

Inflammatory responses play an extraordinary role in the pathogenesis of cerebrovascular and neurological disorders. Baicalin is one of the important flavonoids, which is extracted from Scutellaria baicalensis Georgi. Recently, numerous in vivo and in vitro studies have shown that baicalin has salutary effects for anti-inflammatory and immunomodulatory and has been demonstrated to exert beneficial therapeutic properties in cerebrovascular and neurological diseases. In this review, we aim to discuss that baicalin exerts anti-inflammatory effects through multiple pathways and targets, thus affecting the production of a variety of inflammatory cytokines and neuroprotective process of neurological diseases; furthermore, the related targets of the anti-inflammatory effects of baicalin were analyzed via using the tools of network pharmacology, to provide theoretical basis and innovative ideas for the future clinical application of baicalin.

A Pooled Analysis of the Prognostic Significance of Brugada Syndrome with Atrial Fibrillation.

BACKGROUND: Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF. METHODS: We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events. RESULTS: BrS patients with AF in all studies (OR 1.92, 95% CI:0.91to 4.04, P =0.09; Heterogeneity: P = 0.03, I2=61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P=0.91; Heterogeneity: P = 0.006, I2=80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P=0.002; Heterogeneity: P = 0.40, I2=0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001). CONCLUSION: On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.

Regulatory Mechanisms of the NLRP3 Inflammasome, a Novel Immune-Inflammatory Marker in Cardiovascular Diseases.

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As a macromolecular complex, the NLRP3 inflammasome is activated to produce downstream factors, including caspase-1, IL-1ß, and IL-18, which then promote local inflammatory responses and induce pyroptosis, leading to unfavorable effects. A growing number of studies have examined the relationship between the NLRP3 inflammasome and cardiovascular diseases (CVDs). However, some studies have shown that the NLRP3 inflammasome is not involved in the occurrence of certain diseases. Therefore, identifying the mechanism of action of the NLRP3 inflammasome and its potential involvement in the pathological process of disease progression is of utmost importance. This review discusses the mechanisms of NLRP3 inflammasome activation and the relationship between the inflammasome and CVDs, including coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies, and arrhythmia, as well as CVD-related treatments.

Efficacy and Safety of NaoShuanTong Capsule in the Treatment of Ischemic Stroke: A Meta-Analysis.

Background: Ischemic stroke (IS) is a leading cause of death and long-term disability worldwide. The NaoShuanTong capsule (NSTC), a traditional Chinese patent medicine, has been extensively used in the treatment of stroke in China. However, the clinical efficacy and safety of this treatment has not been statistically and systematically verified by any comprehensive pooled analysis. We therefore performed a meta-analysis to evaluate the efficacy and safety of NSTC in the treatment of IS. Methods: Randomized controlled trials (RCTs) of NSTC in the treatment of IS conducted before September 2018 were retrieved from five databases, according to specific inclusion and exclusion criteria. Two investigators independently reviewed the included studies and extracted relevant data. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook, and analyzed using Review Manager 5.3 software. Results: Thirteen RCTs comprising a total of 1,360 participants were included in this study. NSTC was shown to significantly improve the overall response rate (OR = 3.04, 95% CI [1.76, 5.26], P < 0.00001), and neurological function (NSTC increased Modified Barthel Index (MD = 8.15, 95% CI [3.79, 12.52], P = 0.0005), Functional Independence Measure (MD = 29.61, 95% CI [10.11, 49.10], P = 0.003) and European Stroke Scale scores (MD = 8.51, 95% CI [7.00, 10.01], P = 0.03). In addition, NSTC significantly increased serum adiponectin level (MD = 0.66, 95% CI [0.23, 1.08], P = 0.002). Moreover, NSTC reduced atherosclerotic plaque area (MD = -2.24, 95% CI [-4.02, -0.46], P = 0.01) and intima-media thickness (MD = -0.09, 95% CI [-0.13, -0.05], P < 0.0001). However, there was no significant difference between NSTC treatment and conventional therapy with respect to Fugl-Meyer Assessment score (MD = 10.59, 95% CI [-1.78, 22.96], P = 0.09) or Crouse score (MD = -0.78, 95% CI [-1.79, -0.22], P = 0.13). Conclusions: The results of this meta-analysis showed that NSTC exhibits efficacy in the treatment of cerebral infarction. NSTC can improve the overall response rate and neurological function, increase blood adiponectin, reduce neurological deficits, and decrease atherosclerotic plaque area.

Gender Differences in Prognosis and Risk Stratification of Brugada Syndrome: A Pooled Analysis of 4,140 Patients From 24 Clinical Trials.

Background: Male gender has been consistently shown to be a risk factor for a greater number of arrhythmic events in patients with Brugada Syndrome (BrS). However, there have been no large-scale comprehensive pooled analyses to statistically and systematically verify this association. Therefore, we conducted a pooled analysis on gender differences in prognosis and risk stratification of BrS with a largest sample capacity at present. Methods: We searched PubMed, Embase, Medline, Cochrane Library databases, Chinese National Knowledge Infrastructure, and Wanfang Data for relevant studies published from 2002 to 2017. The prognosis and risk stratification of BrS and risk factors were then investigated and evaluated according to gender. Results: Twenty-four eligible studies involving 4,140 patients were included in the analysis. Male patients (78.1%) had a higher risk of arrhythmic events than female patients (95% confidence interval: 1.46-2.91, P < 0.0001). Among the male population, there were statistical differences between symptomatic patients and asymptomatic patients (95% CI: 2.63-7.86, P < 0.00001), but in the female population, no statistical differences were found. In the female subgroup, electrophysiological study (EPS) positive patients had a tendency toward a higher risk of arrhythmic events than EPS-negative patients (95% CI: 0.93-29.77, P = 0.06). Conclusions: Male patients are at a higher risk of arrhythmic events than female patients. Within the male population, symptomatic patients have a significantly higher risk profile compared to asymptomatic patients, but no such differences are evident within the female population. Consequently, in the female population, the risk of asymptomatic patterns cannot be underestimated.

The Mechanism of Exosomes Function in Neurological Diseases: A Progressive Review.

Exosomes are extracellular microparticles (≈30-100 nm in diameter) secreted from nearly all types of cells, containing a whole set of biological information including proteins, ribonucleic acid (RNA) and lipids. Latest studies show that exosomes contribute to cell-cell communication and are considered closely related with the modulation of angiogenesis and neurogenesis in many neurological diseases. In the past decade, numerous researchers were devoted to exosomes study, but the mechanism of exosomes function and delivery is uncertain. In this review, we summarized several potential mechanisms of exosomes function in angiogenesis, neurogenesis and Blood Brain Barrier (BBB) delivery, and differentiate various sources of exosomes in stroke, tumor, Traumatic Brain Injury (TBI) and Alzheimer's Disease (AD) aimed to report the most advanced mechanical theories in related past three years to provide a new sight for this research area.

Mitochondria and the Pathophysiological Mechanism of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common and significant cardiac arrhythmia in clinical practice, however the pathophysiological mechanism of AF has not been fully explained. At present, there are no available treatment options that can target the underlying pathophysiological processes of AF. Research on improving management strategies for AF can start with a further understanding of the changes of cells in AF. Mitochondria play central roles in the function of cardiac myocytes and many of the pathophysiological processes implicated in AF are relative to mitochondrial function, including formation of reactive oxygen species (ROS), calcium homeostasis, and alterations of oxygen consumption. The changes of levels of phosphocreatine, electron transfer chain proteins and differences in mitochondrial distribution further imply that mitochondria play a role in AF. Related studies of recent years are summarized, in order to elucidate the causal relationship between mitochondria and AF, and provide potential therapeutic target for the treatment and prevention of AF in clinical practice. In the article, we summarize the direct or indirect factors that affect mitochondria function and thus cause AF, including anticancer agents, surgery, gene, age, air pollution, oxidative stress, and ß3-adrenoceptor (ß3-AR). There is a close relationship between mitochondrial dysfunction and the occurrence of AF, which cannot be ignored, and further research in this area is needed.

Mechanisms and Treatments of Oxidative Stress in Atrial Fibrillation.

Atrial fibrillation (AF) is a frequent cardiac arrhythmia. It is a common major cause of serious diseases and is an increasing health-care burden. AF is associated with an excess amount of reactive oxygen species. In this review, we summarize several possible reactive oxygen species pathways that induce AF based on atrial electrical and structural remodeling data. The sources and factors implicated in AF-related oxidative stress include NADPH oxidase activation, calcium overloading and mitochondrial damage, angiotensin system activation, nitric oxide synthase uncoupling, and xanthine oxidase activation-associated cardiovascular conditions. Scavenging oxidative stress markers and related substances are essential aspects of these molecular mechanisms, and may be a therapeutic target in AF.

Anticancer Therapy-Induced Atrial Fibrillation: Electrophysiology and Related Mechanisms.

Some well-established immunotherapy, radiotherapy, postoperation, anticancer drugs such as anthracyclines, antimetabolites, human epidermal growth factor receptor 2 blockers, tyrosine kinase inhibitors, alkylating agents, checkpoint inhibitors, and angiogenesis inhibitors, are significantly linked to cardiotoxicity. Cardiotoxicity is a common complication of several cancer treatments. Some studies observed complications of cardiac arrhythmia associated with the treatment of cancer, including atrial fibrillation (AF), supraventricular arrhythmias, and cardiac repolarization abnormalities. AF increases the risk of cardiovascular morbidity and mortality; it is associated with an almost doubled risk of mortality and a nearly 5-fold increase in the risk of stroke. The occurrence of AF is also usually researched in patients with advanced cancer and those undergoing active cancer treatments. During cancer treatments, the incidence rate of AF affects the prognosis of tumor treatment and challenges the treatment strategy. The present article is mainly focused on the cardiotoxicity of cancer treatments. In our review, we discuss these anticancer therapies and how they induce AF and consequently provide information on the precaution of AF during cancer treatment.